Foretinib

GlaxoSmithKline has revealed its enthusiasm for a new cancer compound being developed by Exelixis by asking to review its partner’s drug before it reaches proof-of-concept. Exelixis says that it has agreed to a request from GSK to initiate its review of XL880 before the compound reaches proof-of-concept. The US biotechnology company says it will “deliver the appropriate diligence information” to the drugs giant in mid-September, at which point GSK will begin its review to decide whether or not to select XL880 for further development. Under the terms of a pact signed between the companies in 2002, GSK can review Exelixis's drugs before they move onto large-scale clinical trials and can choose to fund late-stage testing of up to three possible treatments. It would normally review a drug once proof-of-concept data became available, and indeed GSK recently turned down the chance to co-develop a lung-cancer treatment, hence the interest the XL800 announcement has aroused. To date, GSK has not selected any drugs yet from Exelixis to fund in late-stage trials. This could be about to change, however, and Exelixis chief executive George Scangos said that GSK’s request reflects “the high level of excitement around both the compound and the therapeutic potential of MET (which is involved in tumour growth and angiogenesis) inhibition." He added that recently reported data from the Phase I trial of the drug “underscore our belief that XL880 is the most advanced MET inhibitor in clinical development and we and GSK are committed to building upon this leadership position”. Exelixis says that XL880 has attractive pharmaceutical properties, with high solubility and oral bioavailability, noting that in preclinical studies, it inhibited its targets with nanomolar potency, and retained potent activity against mutationally activated forms of MET found in hereditary papillary renal cell carcinomas. The compound also demonstrated dose-dependent tumour growth inhibition in breast, colorectal and non-small cell lung cancers, plus glioblastoma, and been shown to cause substantial tumour regression in all models tested. The firm added that “significantly, a single dose of XL880 completely inhibited tumour growth for 21 days in a glioblastoma model”. GSK has still to review the drug and Piper Jaffray analyst Edward Tenthoff issued a note saying that it "could still choose to pass on XL880," but he believes "this request indicates the high level of interest GSK holds in this drug”.